Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death

@article{Shi2015CleavageOG,
  title={Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death},
  author={Jianjin Shi and Yue Zhao and Kun Wang and Xuyan Shi and Yue Wang and Huanwei Huang and Yinghua Zhuang and Tao Cai and Fengchao Wang and Feng Shao},
  journal={Nature},
  year={2015},
  volume={526},
  pages={660-665}
}
Inflammatory caspases (caspase-1, -4, -5 and -11) are critical for innate defences. [] Key Method Here we identify gasdermin D (Gsdmd) by genome-wide clustered regularly interspaced palindromic repeat (CRISPR)-Cas9 nuclease screens of caspase-11- and caspase-1-mediated pyroptosis in mouse bone marrow macrophages. GSDMD-deficient cells resisted the induction of pyroptosis by cytosolic lipopolysaccharide and known canonical inflammasome ligands. Interleukin-1β release was also diminished in Gsdmd−/− cells…

Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin

It is shown that GSDME, which was originally identified as DFNA5 (deafness, autosomal dominant 5), can switch caspase-3-mediated apoptosis induced by TNF or chemotherapy drugs to pyroptosis, suggesting that casp enzyme activation can trigger necrosis by cleaving G SDME and offer new insights into cancer chemotherapy.

SERPINB1-mediated checkpoint of inflammatory caspase activation

The results reveal that SERPINB1 acts as a vital gatekeeper of inflammation by restraining neutrophil serine proteases and inflammatory caspases in a genetically and functionally separable manner.

Immunology: Caspase target drives pyroptosis

Two groups report that cleavage of the caspase substrate gasdermin D is sufficient to trigger pyroptosis, a form of programmed necrotic cell death, and are protected from a lethal dose of lipopolysaccharide.

The killer protein Gasdermin D

The evidence to support GSDMD-NT pore formation in eukaryotic cells driving pyroptosis is compelling and an intriguing possibility suggested by Liu et al is that GSD MD-NT is also bactericidal and is able to kill different species of bacteria.

Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor

A GSDMD-derived inhibitor, N-acetyl-Phe-Leu-Thr-Asp-chloromethylketone (Ac-FLTD-CMK), inhibits G SDMD cleavage in vitro and suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes, as well as reduces IL-1β release following activation of the NLRP3 inflammaome in macrophages.

Structural Mechanism for GSDMD Targeting by Autoprocessed Caspases in Pyroptosis

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